Viridian Announces Positive Data from Ongoing Phase 1/2 Trial Evaluating Low Dose VRDN-001 in Patients with Thyroid Eye Disease (TED)

Viridian Therapeutics announced positive topline clinical data from the third, low dose cohort in its ongoing phase 1/2 clinical trial of VRDN-001, an anti-insulin-like growth factor 1 receptor (IGF-1R) antibody, in patients with active thyroid eye disease (TED). The company said it believes this data further validate the differentiated and potentially best-in-class clinical activity of VRDN-001. The data also support the planned dosing interval for Viridian’s VRDN-002 and VRDN-003 subcutaneous programs of up to once monthly.    

“The rapid and meaningful improvements in signs and symptoms of TED observed with a low dose of VRDN-001 reinforce previously reported findings in this trial, and suggest that VRDN-001 may offer a differentiated efficacy profile,” Roger Turbin, MD, Professor of Ophthalmology and Visual Science within the Department of Ophthalmology of Rutgers New Jersey Medical School, and an investigator on the VRDN-001 trial, said in a company news release. “The data also support development of VRDN-001 as a patient-friendly low volume subcutaneous injection, which could reduce the burden of care for patients suffering from TED.”

VRDN-001 – Phase 1/2 Proof-of-Concept Trial

The proof-of-concept portion of this double-blind, placebo-controlled phase 1/2 trial evaluated two infusions of VRDN-001 administered intravenously, 3 weeks apart, with efficacy measured 6 weeks after the first dose. VRDN-001 was evaluated at doses of 3, 10, and 20 mg/kg, with each cohort designed to include six patients randomized to drug, and two patients randomized to placebo. The company previously announced positive results from the first two dose cohorts, which demonstrated a favorable safety profile. The third cohort evaluated a VRDN-001 dose of 3 mg/kg with 6-week data announced today. In the 3 mg/kg dose cohort, nine patients were randomized to receive VRDN-001 to enable all consented patients who were eligible following screening to participate in the trial, and two patients were randomized to receive placebo. One patient receiving placebo discontinued in the trial prior to the 6-week evaluation.

VRDN-001 – Safety Data 

VRDN-001 was generally safe and well-tolerated by all patients treated in the three dose cohorts. There were no reported serious adverse events (SAEs), no discontinuations, and no infusion reactions in patients treated with VRDN-001 as of December 19, 2022, the most recent cut-off date for follow-up observation. The safety and tolerability profile at the 3 mg/kg dose level was generally consistent with previously reported results.

VRDN-001 – Clinical Activity Data

All VRDN-001 treated patients (n=21) in the 3 mg/kg (n=9), 10 mg/kg (n=6) and 20 mg/kg (n=6) cohorts were treated for two full cycles and were evaluated for changes in proptosis, clinical activity score (CAS) and diplopia. Improvement in proptosis and CAS was generally consistent across the three cohorts. A preliminary analysis of systemic IGF-1 levels, a biomarker for target engagement, shows a similar increase was also observed across the three cohorts. The following activity was observed in the 3mg/kg cohort (n=9) and across all three dose groups (n=21) at week 6:

Proptosis

• Proptosis responder rate, defined as a ≥2-millimeter (mm) reduction in proptosis from baseline as measured by exophthalmometry 
  • 67% in the 3mg/kg cohort
  • 71% across all three dose groups
• Mean reduction in proptosis from baseline as measured by exophthalmometry 
  • 2.7 mm in the 3mg/kg cohort
  • 2.3 mm across all three dose groups
• Mean reduction in proptosis from baseline as measured by blinded, centrally reviewed magnetic resonance imaging (MRI) 
  • 2.8 mm in the 3mg/kg cohort (MRI available for 7 patients)
  • 2.76 mm across all three dose groups (MRI available for 16 patients)

Clinical Activity Score (CAS)

• Mean reduction in CAS from baseline on a 7-point measure of signs and symptoms of TED 
  • 4.2-points in the 3mg/kg cohort
  • 4.1-points across all three dose groups
• Maximal or near-maximal therapeutic effect on CAS, defined as reaching a CAS of 0 or 1 on the 7-point composite measure of signs and symptoms of TED 
  • 67% in the 3mg/kg cohort
  • 62% across all three dose groups

Overall response

• Overall responder rate, defined as a ≥2 mm reduction in proptosis and a ≥2 point reduction in CAS 
  • 56% in the 3mg/kg cohort
  • 67% across all three dose groups

Diplopia

• Complete resolution of diplopia, defined as patients with baseline diplopia who achieved a score of 0 on the Gorman subjective diplopia scale 
  • 20% in the 3mg/kg cohort (5 patients with diplopia at baseline)
  • 54% across all three dose groups (13 patients with diplopia at baseline)

“Data from this low dose cohort expand our overall data set to 21 drug-treated patients and build additional confidence in our ongoing phase 3 ‘THRIVE’ trial evaluating VRDN-001 in patients with active TED,” said Barrett Katz, MD, MBA, Chief Medical Officer at Viridian. “This low dose data also increases our confidence in our planned subcutaneous program, which we are advancing as a convenient, self-administered pen.”

Subcutaneous program

Viridian believes that data from the 3 mg/kg dose cohort of VRDN-001 validate a low volume, subcutaneous product profile for the company’s next-generation half-life extended anti-IGF-1R antibodies VRDN-002 and VRDN-003.

VRDN-002 is a novel anti-IGF-1R monoclonal antibody that incorporates half-life extension technology. The company previously reported that VRDN-002 demonstrated a half-life up to 43 days in healthy volunteers, supporting administration as a low-volume, subcutaneous injection up to once-monthly.

VRDN-003 is an anti-IGF-1R monoclonal antibody with the same amino acid sequence as VRDN-001, except for the addition of the half-life extension technology that is incorporated in VRDN-002.

The company’s updated pharmacokinetic (PK) modeling support feasibility of ongoing development of a self-administered pen for subcutaneous administration, and a planned dosing interval of up to once-monthly for VRDN-002 and VRDN-003.

A presentation of the VRDN-001 3 mg/kg data is available under “Events and Presentations” on the Investors section of the Viridian website at viridiantherapeutics.com.

Upcoming corporate priorities

• Initial VRDN-001 results from a proof-of-concept study in patients with chronic TED are expected in the first half of 2023
• VRDN-003 IND filing with the FDA is planned for the second quarter of 2023, with phase 1 results in healthy volunteers expected in the fourth quarter of 2023
• VRDN-002 results in patients with active TED are expected in the second half of 2023
• The company expects to select either the VRDN-002 or VRDN-003 subcutaneous program to advance to a pivotal phase 3 trial in early 2024
• Patient enrollment in the global THRIVE phase 3 trial in patients with active TED is ongoing and results are expected mid-2024